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16th International HIV Drug Resistance Workshop12-16 June 2007, Barbados |
PREVALENCE OF MINORITY QUASISPECIES OF DRUG-RESISTANT HIV-1 IN PATIENTS WITH PRIMARY HIV-1 INFECTION IN ZURICH IN THE YEARS 2002–2006
Antivir Ther. 2007; 12:S47 (abstract no. 40)
KJ Metzner
1, P Rauch1, V von Wyl2, H Kuster2, H-J Stellbrink3, J Böni4, A Trkola2, R Weber2 and HF Günthard2
1University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Erlangen, Germany; 2University Hospital Zurich, Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Switzerland; 3University Hospital Hamburg, Department of Medicine and Institute for Infection Medicine, Hamburg, Germany 4Swiss National Reference Center for Retroviruses, University of Zurich, Zurich, Switzerland
BACKGROUND: On average, 10–15% of patients with primary HIV-1 infection (PHI) are infected with drugresistant viruses in Europe when using population sequencing. We have previously shown that this rate is already doubled in patients from Germany when allele-specific real-time PCR (AS-PCR) is applied to detect minority quasispecies of viruses harboring the K103N and/or the M184V mutation. Based on population sequencing, the transmission rate of drug-resistant variants is lower in Zurich compared with other European areas. Thus, we expanded our study and measured the prevalence of minority quasispecies of the K103N and M184V reverse transcriptase mutations in the Zurich-PHI-study.
METHODS: Seventy-four patients with documented PHI from Zurich, Switzerland were included in this study. Patients were identified between March 2002 and July 2006, and none received antiretroviral therapy (ART) prior to sampling. Minority quasispecies of K103N or M184V variants were quantified by AS-PCR with an approximate discriminative power between 0.01 and 0.2%.
RESULTS: Conventional population sequencing was performed in all patients and neither the K103N nor the M184V mutation was detected in any patient. Two patients harboured PI-resistant HIV-1 and TAMs were detected in another patient. In contrast, both mutations were frequently detected using AS-PCR: the K103N mutation was found in 4/74 patients (5.4%) ranging from 0.18 ±0.02% to 3.76 ±0.79%, and M184V variants were detected in 11/74 patients (14.9%) in a frequency of 0.4 ±0.1% to 8.3 ±2.2%. Two of those patients were harboring both drug-resistant variants, thus, in total, AS-PCR revealed the presence of drug-resistant variants in 13/74 patients with PHI (17.6%) prior to ART. Nine of those 13 patients received boosted protease inhibitor containing ART for ≥10 months and up to 4 years and none of them experienced therapy failure thus far.
CONCLUSIONS: The prevalence of minority quasispecies of K103N and M184V variants is high in patients with PHI from Zurich, thus, the transmission rate of drug-resistant viruses is probably underestimated based on population sequencing. However, detection of minority quasispecies of drug-resistant HIV-1 was not associated with therapeutic failure in those patients within 0.8 to 4 years.
2007-06-12
40
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